Pembrolizumab and stereotactic body radiotherapy combined in advanced hepatocellular carcinoma post sorafenib – A phase II trial (PEMRAD)

作者：Grainne M. O’Kane, Aruz Mesci, Raymond Jang, Aisling Barry, Cynthia M Bocaya, Giselle M. Boukhaled, Holly J. Acton, D. Doddington, Rowena Rodrigo, Leo M.L. Chan, Babak Noamani, Harry Harvey, Andrés Elía, Rhoda Law, Rebecca M. Prince, Mark Doherty, Anna Dodd, David Wong, Lisa Wang, B.X. Wang, E.X. Chen, Laura A. Dawson, J. J. Knox · 发表于：JHEP Reports · 年份：2025 · DOI：10.1016/j.jhepr.2025.101658 · 被引用次数：6 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cancer Immunotherapy and Biomarkers、Cholangiocarcinoma and Gallbladder Cancer Studies

Background There is strong rationale for integrated approaches of immune-checkpoint inhibitors and locoregional therapies in hepatocellular carcinoma (HCC). Methods The PEMRAD phase II trial investigated the combination of pembrolizumab and stereotactic body radiation (SBRT) in patients with advanced HCC following progression on sorafenib. Patients received pembrolizumab on day 1 and SBRT commenced Day 2. Up to 10 hepatic lesions (<20cm) were treated with SBRT. Pembrolizumab was continued every 21 days until progression, unacceptable toxicity or withdrawal. The primary endpoint was objective response rate (ORR) as measured by RECIST v1.1, hypothesizing an increase to 40% with the combination. Tissue and liquid biopsies were collected for correlative analyses including immunohistochemistry, longitudinal blood Cytometry by Time-Of-Flight, and serum cytokines. Results Between March 2018 and March 2023, 18 patients of a planned 22 were enrolled,11 (61%) with macrovascular invasion (MVI) and 15 (83%) with extrahepatic metastases. Viral hepatitis was the underlying etiology in 50%. The ORR was 41%(95% CI 18-67%). The median progression free survival was 5.4 (2.8-9.9) months and median overall survival was 12.6 (5.7-25.8) months. Of 34 liver lesions treated with SBRT, only 3 progressed in 2 patients. Of the 11 patients with MVI, 5 (45%) had evidence of a response, including 1 complete response. Treatment related adverse events ≥ grade 3 were reported in 4 patients (22%). One death d...